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Plasticity of melanoma in vivo: murine lesions resulting from Trp53, but not Cdk4 or Arf deregulation, display neural transdifferentiation

Citation

Handoko, HY and Boyle, GM and Ferguson, B and Muller, HK and Soyer, HP and Walker, GJ, Plasticity of melanoma in vivo: murine lesions resulting from Trp53, but not Cdk4 or Arf deregulation, display neural transdifferentiation, Pigment Cell and Melanoma Research, 26, (5) pp. 731-734. ISSN 1755-1471 (2013) [Refereed Article]

Copyright Statement

Copyright 2013 John Wiley & Sons A/S

DOI: doi:10.1111/pcmr.12124

Abstract

We previously noted that melanomas developing in Cdk4R24C/R24C::Tyr-NRAS, Arf−/−::Tyr-NRAS and Trp53F/F::Tyr-Cre(ER)::Tyr-NRAS mice exhibited differences in behaviour in vivo. We investigated this phenomenon using global gene expression profiling of lesions from the respective genotypes. While those from the Cdk4- and Arf-mutant mice exhibited similar profiles, the Trp53F/F::Tyr-Cre(ER)::Tyr-NRAS melanomas were strikingly different, showing relative down-regulation of melanocyte-related genes, and up-regulation of genes related to neural differentiation. Specifically, they highly expressed genes representative of the myelin-producing peripheral oligodendrite (Schwann cell) lineage, although histopathologically the lesions did not exhibit the classical features of schwannoma. As Schwann cell precursors can be a cellular origin of melanocytes, it is unsurprising that plasticity with respect to melanocyte-neural differentiation can occur in melanoma. What is surprising is the genotype proclivity. Comparison of gene expression signatures revealed that melanomas from the Trp53-mutant mice show significant similarities with a subset of aggressive human melanomas with relatively low levels of MITF.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Oncology and Carcinogenesis
Research Field:Cancer Cell Biology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Skin and Related Disorders
Author:Muller, HK (Professor Konrad Muller)
ID Code:88737
Year Published:2013
Web of Science® Times Cited:6
Deposited By:Medicine (Discipline)
Deposited On:2014-02-13
Last Modified:2014-05-15
Downloads:0

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